POS0292 INCREASE OF PRO-INFLAMMATORY CYTOKINES IS ASSOCIATED WITH ANTI-IDIOTYPE EVENTS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH INFLIXIMAB OR ADALIMUMAB
Authors: D. X. Xibille Friedmann, S. M. Carrillo Vazquez, J. González Christen, D. Vega Morales, M. Garza Elizondo, R. Hernández, J. E. Ortíz Panozo, J. L. Montiel Hernández
Journal: Annals of the Rheumatic Diseases (2022)

Background A significant percentage of rheumatoid arthritis (RA) patients undergoing Infliximab (IFX) or Adalimumab (ADA) treatment develop antidrug antibodies with potential negative effects over their clinical activity; however, it is unknown if these anti-idiotype events could be associated with changes in cytokines levels Objectives To evaluate the association between blood cytokine levels, anti-idiotype events and clinical activity in RA patients treated with IFX or ADA. Methods All patients complied with ACR/EULAR 2021 criteria for RA and received anti-TNFa agents. Blood samples were collected during the drug trough and kept at -75ºC until analysis. Clinical activity was based on DAS28-ESR. Specific anti-drug antibodies to IFX and ADA were evaluated by sandwich ELISA. Cytokine blood levels were quantified using a multiplex system or sandwich ELISA. Results 57 patients with RA were recruited, 17 treated with IFX and 40 with ADA. According to the presence of anti-drug antibodies and sub-optimal levels of the biologic drug, patients were classified as immunogenic (29.8%; n=17) and non-immunogenic (70.2%; n=40), the first showed significantly higher ESR (p&lt;0.001) and DAS28 (p&lt;0.005). A significant association was seen between antidrug antibodies and increases of IFNg (2.1 OR, CI95%:1.2-3.8, p&lt;0.01); MCP-1 (3.9 OR, CI95%:1.1-14.5, p&lt;0.05); MIF (2.8 OR, CI95%:1.3-5.7, p&lt;0.01) and TNFa 3.0 OR, CI95%:1.3-6.6, p&lt;0.01 (see Table 1). Although anti-idiotype events were more frequent in IFX treated patients (41%), a significant difference was not seen when comparing with ADA treated patients (25%). Table 1. Association analysis between anti-Idiotype events with cytokine levels. Anti-Idiotype events vs Crude results OR (IC, 95%) p Model 1* OR (IC, 95%) p Model 2** OR (IC, 95%) p IL-1β 2.04 (1.26-3.30 ) 0.004 2.18 (1.27-3.74 ) 0.005 2.72 (1.41-5.24 ) 0.003 IL-6 1.29 (1.02-1.64 ) 0.03 1.30 (1.00-1.69 ) 0.04 1.33 (1.03-1.72 ) 0.02 IL-8 1.20 (0.80-1.79) 0.37 1.24 (0.81-1.88) 0.32 1.22 (0.79-1.90) 0.35 IL-10 1.18 (0.91-1.51) 0.20 1.16 (0.89-1.53) 0.26 1.22 (0.92-1.62) 0.15 IL-12p40 1.73 (1.09-2.76 ) 0.02 1.67 (1.00-2.80 ) 0.04 1.90 (1.12-3.22 ) 0.01 IL-17A 1.39 (0.95-2.02) 0.08 1.31 (0.90-1.91) 0.15 1.51 (1.01-2.25 ) 0.04 INF ϒ 2.38 (1.37-4.12 ) 0.002 2.36 (1.32-4.23 ) 0.004 2.97 (1.57-5.61 ) 0.001 Leptina 6.15 (0.77-48.72) 0.09 4.79 (0.63-1.07) 0.12 7.30 (0.78-68.37) 0.08 MIF 3.94 (1.07-14.48 ) 0.04 5.86 (1.28-26.65 ) 0.02 3.45 (0.87-13.68) 0.07 MCP-1 2.98 (1.34-6.62 ) 0.007 3.28 (1.38-7.78 ) 0.007 3.74 (1.47-9.49 ) 0.005 TNFα 2.79 (1.38-5.63 ) 0.004 2.55 (1.27-5.14 ) 0.008 2.72 (1.30-5.71 ) 0.008 Anti-Idiotype events vs Crude results *** OR (IC, 95% ) p Model 1 * OR (IC, 95% ) p Model 2 ** OR (IC, 95% ) p IL-1β 1.07 (1.02-1.12) 0.004 1.08 (1.02-1.13) 0.005 1.10 (1.03-1.17) 0.003 IL-6 1.02 (1.00-1.05) 0.03 1.02 (1.00-1.05) 0.04 1.02 (1.00-1.05) 0.02 IL-8 1.02 (0.98-1.06) 0.37 1.02 (0.98-1.06) 0.32 1.01 (0.97-1.06) 0.35 IL-10 1.02 (0.99-1.04) 0.20 1.01 (0.99-1.04) 0.26 1.01 (0.99-1.04) 0.15 IL-12p40 1.05 (1.01-1.10) 0.02 1.05 (1.00-1.10) 0.04 1.06 (1.01-1.11) 0.01 IL-17A 1.03 (0.99-1.07) 0.08 1.03 (0.99-1.06) 0.15 1.03 (1.00-1.08) 0.04 INF ϒ 1.09 (1.03-1.14) 0.002 1.08 (1.02-1.14) 0.004 1.10 (1.04-1.17) 0.001 Leptina 1.19 (0.98-1.45) 0.09 1.16 (0.95-1.40) 0.12 1.20 (0.97-1.49) 0.08 MIF 1.14 (1.01-1.29 ) 0.04 1.18 (1.02-1.36 ) 0.02 1.12 (0.98-1.28) 0.07 MCP-1 1.11 (1.03-1.20) 0.007 1.12 (1.03-1.21 ) 0.007 1.13 (1.03-1.23 ) 0.005 TNFα 1.10 (1.03-1.18) 0.004 1.09 (1.02-1.16) 0.008 1.10 (1.02-1.18) 0.008 *Model 1: Adjusted by age + Body mass index; **Model 2: Adjusted by Time since onset of disease + Time with biologic + complementary treatment with MTX; ***Adjusted to 10% increase of cytokine. Conclusion Patients with antidrug antibodies to IFX or ADA had higher ESR and DAS28 and a showed a significant association with higher levels of IFNg, MCP-1, MIF and TNFa. References [1]Parikh CR, Ponnampalam JK, Seligmann G, et al. Therapeutic Advances in Musculoskeletal Disease. 2021. doi:10.1177/1759720X211002685 Disclosure of Interests Daniel Xavier Xibille Friedmann Speakers bureau: Lilly, Abbvie, Paid instructor for: Lilly, Abbvie, Consultant of: Lilly, Abbvie, Sandra Miriam Carrillo Vazquez Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Judith González Christen: None declared, David Vega Morales Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Mario Garza Elizondo Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Ramiro Hernández: None declared, José Eduardo Ortíz Panozo: None declared, José Luis Montiel Hernández: None declared